[unreadable] This is an application for continuation of funding for the Cleveland Pediatric Pharmacology Research Unit (PPRU). Our unit was first funded in 1994, one year after the establishment of the PPRU and has been funded since then at a level one-half to two thirds that of the other units in the network. Despite this funding bias, Cleveland has been an active member of the Network. During the first four years we participated in 13 network protocols contributing 298 patients. The last five years have seen this trajectory in activity maintained. We have been the lead site on 28 protocols and participated overall in 69 network studies enrolling more than 657 children. We have also completed two major multisite studies designed and coordinated by the Cleveland PPRU that have subsequently been adopted by the drugs' innovators to support SNDA filings. In support of ongoing PPRU activities we have developed two print symposia, one dealing with the evaluation of antihypertensive agents in children and the other dealing with the treatment of sleep disorders in children, designed to set the stage for further clinical trials. Finally we are the lead site on the first PPRU-exclusive multisite R01 application submitted to NIH. Our renewal application both details our accomplishments as a member of the PPRU Network and outlines our plans to expand our research base into several new therapeutic areas. To compliment our demonstrated expertise in pharmacokinetic/ pharmacodynamic modeling we propose a study to evaluate new approaches to study design that should add parsimony to our efforts at pediatric drug development. These approaches will be essential in support of the upcoming PPRU initiatives in response to the Best Pharmaceuticals for Children Act. We will also bring to the network a series of trials in the area of pediatric sleep disorders. We will also present approaches to the integration of pharmacogenetic approaches into the elucidation of novel mechanisms of adverse drug reactions in children. Finally, we will discuss our expanded training program in pediatric pharmacology research. [unreadable] [unreadable]